Research on xenotransplantation has been intensified over the past years to alleviate organ shortage. However, host immune responses present a formidable barrier to transplantation across species. Whereas natural antibodies cause immediate rejection of such discordant transplants, endothelial cell (EC) injury and activation of graft vessel lining EC play a pivotal role in initiating chronic graft rejection. Disruption of the integrity of the endothelial layer is of undoubted importance in numerous conditions, including syngeneic and non-syngeneic tissue transplants as well as infectious, neoplastic, inflammatory and cardiovascular diseases.
Heretofore immunomodulation and transplant acceptance have required reliance on systemically-administered immunosuppressive agents. While such agents permit some degree of transplant acceptance, success is limited and perhaps of more significance, a patient's immune system is thoroughly compromised as a result of such agents. Thus a need still remains for therapeutic materials and treatment paradigms which can achieve immunomodulation absent the toxicity and adverse affects on a patient's immune system.
Similarly, exogenous immunogens or stimuli have posed a clinical challenge. These, too, can result in adverse immunological events or inflammatory reactions which necessitate treatment. Heretofore, clinical management of such adverse events has relied almost exclusively on treatments with pharmaceutical agents which suppress the immune system non-specifically.
Autoimmune diseases and other similar diseases are yet another clinical manifestation of heightened inflammatory reactions or adverse immune responses. Successful management of such diseases has eluded clinicians to date.
An object of the present invention is to provide a tissue engineering solution for achieving immunomodulation without reliance on chemicals or pharmaceuticals which compromise a patient's immune system. This tissue engineering solution can be employed to alter, in a clinically practical manner, an immune response to exogenous and endogenous immunogens, including non-syngeneic as well as syngeneic cell-, tissue- or organ-associated immunogens. Another object of the present invention is to facilitate a patient's acceptance of non-syngeneic as well as syngeneic cells, tissues or organs. Another object of the present invention is to employ this tissue engineering solution to modulate an inflammatory reaction such as that associated with injury and various diseases. Another object is to utilize the materials and methods of the present invention to manage autoimmunity and related diseases.